Reproducible radiomics through automated machine learning validated on twelve clinical applications

Radiomics uses quantitative medical imaging features to predict clinical outcomes. Currently, in a new clinical application, findingthe optimal radiomics method out of the wide range of available options has to be done manually through a heuristic trial-anderror process. In this study we propose a framework for automatically optimizing the construction of radiomics workflows perapplication. To this end, we formulate radiomics as a modular workflow and include a large collection of common algorithms foreach component. To optimize the workflow per application, we employ automated machine learning using a random search andensembling. We evaluate our method in twelve different clinical applications, resulting in the following area under the curves: 1)liposarcoma (0.83); 2) desmoid-type fibromatosis (0.82); 3) primary liver tumors (0.80); 4) gastrointestinal stromal tumors (0.77);5) colorectal liver metastases (0.61); 6) melanoma metastases (0.45); 7) hepatocellular carcinoma (0.75); 8) mesenteric fibrosis(0.80); 9) prostate cancer (0.72); 10) glioma (0.71); 11) Alzheimer’s disease (0.87); and 12) head and neck cancer (0.84). Weshow that our framework has a competitive performance compared human experts, outperforms a radiomics baseline, and performssimilar or superior to Bayesian optimization and more advanced ensemble approaches. Concluding, our method fully automaticallyoptimizes the construction of radiomics workflows, thereby streamlining the search for radiomics biomarkers in new applications.To facilitate reproducibility and future research, we publicly release six datasets, the software implementation of our framework,and the code to reproduce this study

Clinical and therapeutic aspects of extrapulmonary small cell carcinoma

Extrapulmonary small cell carcinoma (EPSCC) is usually treated similarly to small cell lung cancer. Differences in aetiology, clinical course, frequency of brain metastases, and survival, however, warrant a differential therapeutic approach. In this review, we focus on the treatment of the most predominant sites of origin of EPSCC; the gastrointestinal tract, the genitourinary tract, the head and neck region, and small cell carcinoma of unknown primary. Furthermore we review the available data concerning the controversial issue of prophylactic cranial irradiation (PCI) after optimal treatment of EPSCC. We found in the literature a significant lower incidence of brain metastases in EPSCC as compared to pulmonary small cell carcinoma when PCI is omitted and therefore we do not recommend PCI. An exception is EPSCC originating from the head and neck region which is associated with a higher incidence of brain metastasis, justifying addition of PCI. (C) 2008 Elsevier Ltd. All rights reserved

A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer

The efficacy and side-effects of megestrol acetate and medroxyprogesterone acetate in postmenopausal patients with advanced breast cancer were compared in a prospectively randomized study. The dosage of MA was 2 × 80 mg p.o. or MPA 2 × 500 mg p.o. daily, given as a secondary hormonal treatment, mostly after previous treatment with tamoxifen. Ninety-eight patients entered the study and 92 were evaluable for effect, 48 patients on MA and 44 on MPA. Age, main tumor site and prior treatment were not different, but there was a preponderance of ER-negative tumors in the MA group. Responses appeared to be more frequent in the MPA-treated group (25% vs. 43%), predominantly in bone lesions, 12% for MA and 45% for MPA. Median progression-free survival was comparable, 15 vs. 10 months, and overall survival was not different (20 vs. 16 months). Toxicity was frequent, occurring in 83% vs. 74% of patients: increased appetite, nausea and dizziness in more than 20%, and a preponderance of pyrosis and breathlessness on MA and hot flashes, sweating and tremors on MPA. Cushingoid symptoms were present in about a quarter of the patients treated for more than 3 months. The occurrence of thrombo-embolic episodes and cardiovascular events was evenly distributed. Patients on MPA had more often increase in body weight, systolic blood pressure and serum creatinine than those treated with MA. It is concluded that MPA may be more effective for treatment of bone metastases, at the expense of more progestational side-effects. The occurrence of Cushingoid effects is frequent but similar in both arms, while the incidence of cardiovascular or thrombo-embolic events cannot be related to the use of either compound

Clinical and genetic aspects of testicular germ cell tumours

<p>Abstract</p> <p>In this paper we review clinical and genetic aspects of testicular germ cell tumours (TGCTs). TGCT is the most common type of malignant disorder in men aged 15-40 years. Its incidence has increased sharply in recent years. Fortunately, survival of patients with TGCT has improved enormously, which can chiefly be attributed to the cisplatin-based polychemotherapy that was introduced in the nineteen eighties to treat patients with metastasized TGCT. In addition, new strategies have been developed in the surgical approach to metastasized/non-metastasized TGCT and alterations have been made to the radiotherapy technique and radiation dose for seminoma. Family history of TGCT is among the strongest risk factors for this tumour type. Although this fact and others suggest the existence of genetic predisposition to develop TGCT, no germline mutations conferring high risk of developing TGCT have been identified so far. A small deletion, referred to as gr/gr, identified on the Y chromosome is probably associated with only a modest increase in TGCT risk, and linkage of familial TGCT to the Xq27 region has not been confirmed yet. Whether highly penetrant TGCT-predisposing mutations truly exist or familial clustering of TGCT can be explained by combinations of weak predispositions, shared in utero or postnatal risks factors and coincidental somatic mutations is an intriguing puzzle, still waiting to be solved.</p

Cardiotoxicity associated with the use of trastuzumab in breast cancer patients

The monoclonal antibody against HER2, trastuzumab (Herceptin (R)), has become an important player in the treatment of patients with HER2-positive breast cancer. Both in the metastatic and adjuvant setting, the addition of trastuzumab to other systemic treatments has led to a striking increase in tumor response and survival. The downside with the use of this agent, however, is its inherent cardiotoxicity, which is particularly common when anthracyclines are used concurrently. This review will focus on all aspects of the cardiac side-effects of trastuzumab, ranging from epidemiology and pathophysiology to cardiac monitoring, and treatment and prevention

Bleomycin and scuba diving: where is the harm?

Testicular cancer is the most frequent malignant disease in men aged 15–40 years. Due to its sensitivity to chemotherapeutic drugs, most patients, including those with widespread metastatic disease, can now be cured. Bleomycin is an essential component of the most effective chemotherapy regimen for testicular cancer—ie, bleomycin, etoposide, and cisplatin [BEP].1 However, bleomycin is feared for its induction of bleomycin-induced pneumonitis (BIP), which is sometimes fatal.2 After reports in the 1980s of perioperative complications that were ascribed to bleomycin, high inspired-oxygen fractions during anaesthesia were avoided, as were high inspired-oxygen fractions under hyperbaric circumstances, such as scuba diving

The relation between soluble apoptotic proteins and subclinical cardiotoxicity in adjuvant-treated breast cancer patients

Background: Circulating apoptotic proteins are increased in heart failure patients. We evaluated whether circulating soluble apoptosis-related protein levels change after anthracycline-containing chemotherapy and radiotherapy in relation to cardiac dysfunction or the applied treatment. Patients and Methods: Circulating apoptotic proteins were measured with immunoassay in 40 breast cancer patients following surgery (T0), one month (T1) and one year (T2) after epirubicin-based chemotherapy. Standard-dose (n=21) or high-dose (n=19) myeloablative chemotherapy, preceded irradiation and tamoxifen. Circulating apoptotic proteins were compared with previous cardiac evaluations. Results: Soluble tumor necrosis factor receptor 1 (+30%), 2 (+43%) and Fas (+40%) were transiently increased at T-1 compared to T-0, whereas Fas ligand (-64%) was transiently decreased, especially in the high-dose group. Apoptosis markers were not associated with cardiac dysfunction. Conclusion: Significant, but transient changes in soluble apoptotic protein levels were observed, particularly after high-dose chemotherapy. No relation was found between apoptosis-related proteins and cardiotoxicity